Since 1978 the Center for Research on the Etiology and Treatment of Alcohol Dependence (UConn ARC) has been devoted to a systematic exploration of the alcohol dependence syndrome, its etiology, patterning and treatment. This application requests five years of continued funding for the Center's research programs on vulnerability to alcoholism, mechanisms of alcohol dependence, and promising treatment interventions. Component I (Administrative/Scientific Core) describes the UConn ARC's Organizational framework, quality control mechanisms, and core research laboratories. Component II describes the continuation of an ongoing prospective study that is examining the relationship of family history, antisocial personality disorder and gender to measures of cognitive functioning and electrophysiology. This research will evaluate the implication of neurocognitive deficits for pathological alcohol involvement. Three additional components focus on the neurobiology of dependence and neuroadaptation. Component III (Alcohol/Neuroceptor gene expression) will study the cellular and molecular basis of neuronal sensitivity to ethanol. Component IV (concurrent withdrawal) will examine electrophysiological and subjective features of withdrawal from alcohol and cocaine. Component V (Acamprosate mechanisms) will use a laboratory- based alcohol self-administration paradigm to evaluate acamprosate, a promising GABAergic pharmacotherapy, in terms of its effects on impaired control and withdrawal. Two additional components will study treatment efficacy and the mechanisms of treatment response. Component VI (Brief Intervention 3 for Problem Drinkers) will use a highly sophisticated daily monitoring procedure to study how brief interventions modify drinking behavior. Component VII (Depot Naltrexone) will be the first randomized trial to compare oral naltrexone with a long-acting depot formulation designed to increase compliance and the drug's effectiveness, especially with severe alcoholics. A Pilot Studies component (VIII) will support seven studies in three main investigational areas: neuropharmacology/neurobiology (i.e., fMRI), electrophysiology/brain imaging (i.e., basic clinical investigations), and treatment trials (i.e., applied clinical investigations). Finally, this application describes educational activities, information dissemination, conference sponsorships, a visiting scholars program, and consulting work that will strengthen the role of the UConn ARC as a regional and national resource.